Neuropalliative Care Needs Checklist for Motor Neuron Disease and Parkinson's Disease: A Biopsychosocial Approach.

Objectives: Neurodegenerative disorders necessitate comprehensive palliative care due to their progressive and irreversible nature. Limited studies have explored the comprehensive assessment needs of this population. This present study is designed to develop a checklist for evaluating the palliative care needs of individuals with motor neuron disease (MND) and Parkinson's disease (PD). Materials and Methods: The checklist was created through an extensive literature review and discussions with stakeholders in neuropalliative. Feedback from six field experts led to the finalisation of the checklist, which comprised 53 items addressing the unique biopsychosocial needs of MND and PD. Sixty patient-caregiver dyads receiving treatment in a tertiary referral care centre for neurology in south India completed the checklist. Results: People with MND had more identified needs with speech, swallowing, and communication, while people with PD reported needs in managing tremors, reduced movements, and subjective feelings of stiffness. People denying the severity of the illness was found to be a major psychosocial issue. The checklist addresses the dearth of specific tools for assessing palliative care needs in neurodegenerative disorders, particularly MND and PD. By incorporating disease-specific and generic items, the checklist offers a broad assessment of patients' multidimensional needs. Conclusion: This study contributes to the area of neuropalliative care by developing the neuropalliative care needs checklist (NPCNC) as a valuable tool for assessing the needs of individuals with neurodegenerative diseases. Future research should focus on refining and validating the NPCNC with larger and more diverse groups, applicability in different contexts, and investigating its sensitivity to changes over time.

Juvenile Amyotrophic Lateral Sclerosis: A Case Report of a Rare and Aggressive Presentation in a 22-Year-Old Filipino Male.

Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disorder primarily affecting adults, but juvenile-onset ALS is exceptionally rare. We report a rare case of a 22-year-old Filipino male patient who exhibited early-onset weakness, muscle atrophy, and tongue fasciculations, followed by rapidly progressive dysphagia and respiratory distress. Electromyography - Nerve Conduction Velocity (EMG-NCV) findings showed evidence for a chronic, active predominantly motor neuronal-axonal loss type of neuropathy involving the tongue and limb muscles bilaterally consistent with a motor neuron disease. The patient was treated with riluzole with no significant improvement in symptoms. Despite multidisciplinary interventions, the disease rapidly progressed, highlighting the challenges in managing juvenile ALS cases. This case report emphasizes the importance of considering ALS in the differential diagnosis of progressive motor dysfunction in younger patients and the complexities involved in their care.

Exploring the Impact of Personalized Physical Therapy on a Patient With Motor Neuron Disorder: A Case Study.

This case study examines the effect of a tailor-made physiotherapy regimen on an 85-year-old male patient who was suffering from bulbar motor neuron disease (MND) and had a history of stroke and COVID-19. The physiotherapy plan was designed to strategically address the patient's respiratory issues, generalized weakness affecting limb muscles, and speech and swallowing difficulties. Frequent evaluations made it possible to adjust the treatment plan, emphasizing a holistic strategy to improve the patient's overall quality of life. Improvements in scores on multiple functional scales and manual muscle testing were shown by outcome measures and follow-up evaluations. This case emphasizes how important customized physiotherapy is for maximizing functional outcomes and enhancing the quality of life for patients dealing with the complicated conditions of bulbar MND.

Association between motor neuron disease and HIV infection: A systematic review of case reports.

BACKGROUND: Motor neuron disease (MND) is a well-known group of neurodegenerative diseases, with amyotrophic lateral sclerosis (ALS) being the most common form. Since 1985, a possible association between MND/ALS and HIV infection has been described. METHODS: We performed a systematic review of case reports and case series involving people living with HIV with MND/ALS through PubMed, Bireme, Embase, and Lilacs databases. The risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tool for Case Reports. RESULTS: We analyzed 36 articles presenting 88 cases. The mean age was 41.6 years. Antiretroviral therapy (ART) was used by 89.8% and riluzole by 16.9%. First signs and symptoms were similarly present on cervical/upper (25%) and lumbosacral/lower limbs (23.9%), mostly with fasciculations (69.8%) and hyperreflexia (58.8%). MND had a progressive course in 32.9% patients and a clinical improve in 54.6% following ART. The mean survival of the 32 patients who died was 12.3 months and the mean survival of the living patients was 62 months. Respiratory failure was the main cause of death (35.7%). CONCLUSIONS: MND/ALS may present differently in the people living with HIV as a rapidly progressive disease in younger people but with the potential to improve weakness and survival through antiretroviral therapy.

Development and Evaluation of the Telehealth in Motor Neuron Disease System: The TIME Study Protocol.

BACKGROUND: For more responsive care provision for motor neuron disease and caregivers, a digital system called Telehealth in MND-Care (TiM-C) was created. TiM-C sends regular symptom questionnaires to users; their responses are sent to health care professionals (HCPs). To enable people with motor neuron disease to participate in research studies more easily, a parallel platform was developed from TiM-C, called Telehealth in MND-Research (TiM-R). TiM-R can advertise studies, collect data, and make them available to MND researchers. OBJECTIVE: This study has 4 work packages (WPs) to facilitate service approval, codevelop the TiM systems, and evaluate the service. Each WP aims to understand (1) what helps and hinders the approval of the TiM-C system as a National Health Service; (2) what aspects of MND care and research are currently unmet and can be addressed through the TiM-C and TiM-R systems; (3) how TiM-C influences MND care, from the perspective of people with motor neuron disease, their caregivers, and HCPs; and (4) the costs and benefits associated with TiM-C. METHODS: WP1 will use semistructured interviews with 10-15 people involved in the approval of TiM-C to understand the barriers and facilitators to governance processes. WP2 will use individual and group interviews with 25-35 users (people with motor neuron disease, caregivers, HCPs, MND researchers, and industry) of TiM-C and TiM-R to understand the current unmet needs of these user groups and how TiM services can be developed to meet these needs. WP3 will use a process evaluation involving 5 elements; local context, engagement, user experiences, service impact, and mechanisms of action. A range of methods, including audits, analysis of routine data, questionnaires, interviews, and observations will be used with people with motor neuron disease, caregivers, and HCPs, both those using the system and those who declined the service when invited. WP4 will use data collected through the process evaluation and known costs to conduct a cost-consequence and budget impact analysis to explore the cost-benefit of the TiM-C service. Most data collected will be qualitative, with thematic and framework analysis used to develop themes from transcripts and observations. Descriptive statistics or t tests and chi-square tests will be used to describe and analyze quantitative data. RESULTS: This study has received ethical approval and has begun recruitment in 1 site. Further, 13 specialist MND centers will adopt TiM-C and the TIME study, beginning in July 2024. The study will conclude in November 2026 and a final report will be produced 3 months after the completion date. CONCLUSIONS: This study will facilitate the implementation and development of TiM-C and TiM-R and fully evaluate the TiM-C service, enabling informed decision-making among health care providers regarding continued involvement and contribute to the wider literature relating to how technology-enabled care services can affect clinical care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57685.

Neuropathological spectrum of anti-IgLON5 disease and stages of brainstem tau pathology: updated neuropathological research criteria of the disease-related tauopathy.

Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation of a broader spectrum of neuropathologies underlying a particular constellation of clinical symptoms. In this study, we describe the neuropathological findings in 22 patients with anti-IgLON5 disease from 9 different European centers. In 15 patients (68%), we observed a hypothalamic and brainstem-predominant tauopathy of varying severity in which the original research neuropathological criteria were readily applicable. This pathology was observed in younger patients (median age at onset 61 years) with a long disease duration (median 9 years). In contrast, in 7 (32%) patients, the originally described brainstem tauopathy was nearly absent or only minimal in the form of delicate threads, despite mild-to-moderate neurodegenerative features, consistent clinical symptoms and the presence of anti-IgLON5 antibodies in CSF and serum. These patients were older at onset (median 79 years) and had shorter disease duration (median < 1 year). Overall, about one-third of the patients showed concomitant TDP-43 pathology within the regions affected by tau pathology and/or neurodegeneration. Based on these observations and in view of the spectrum of the tau burden in the core regions involved in the disease, we propose a simple staging system: stage 1 mild neurodegeneration without overt or only minimal tau pathology, stage 2 moderate neurodegeneration and mild/ moderate tauopathy and stage 3 prominent neurodegeneration and tau pathology. This staging intends to reflect a potential (age- and time-dependent) progression of tau pathology, supporting the current notion that tau accumulation is a secondary phenomenon related to the presence of anti-IgLON5 antibodies in the CNS. Finally, we adapt the original research criteria of the anti-IgLON5 disease-related tauopathy to include the spectrum of pathologies observed in this larger postmortem series.

Recognized cases of amyotrophic lateral sclerosis in automobile workers by the Korean Epidemiologic Investigation Evaluation Committee.

Background: Three automobile company workers (one from Factory D and two from Factory E) were diagnosed with amyotrophic lateral sclerosis. The Korean Epidemiologic Investigation and Evaluation Committee determined that there is considerable scientific evidence supporting the association between amyotrophic lateral sclerosis and combined exposure to heavy metals, organic solvents, and diesel exhaust at the manufacturing plant. Case presentation: Patient A, who primarily engaged in engine processing and completed vehicle inspection at Factory D, was exposed to considerable amounts of heavy metals and organic solvents during medium- and large-engine processing, welding, and painting for over 23 years. Additionally, the patient was likely exposed to diesel exhaust for 33 years from forklifts delivering engines in the workshop. Patients B and C, who were responsible for engine assembly, ignition testing, and engine shipment at Factory E since around 1990, were exposed to lead and benzene from gasoline during engine ignition tests in the engine department for 15 and 16 years, respectively. They also encountered welding fumes, heavy metals, and organic solvents during welding and painting tasks. In addition, Patients B and C were continuously exposed to diesel exhaust from logistics vehicles on standby during work hours for 25 and 30 years, respectively. Conclusions: Although the specific level of lead exposure causing amyotrophic lateral sclerosis remains undetermined, numerous studies have consistently reported a relationship between lead exposure and disease development. Limited evidence suggests that exposure to organic solvents and diesel exhaust may increase the risk of amyotrophic lateral sclerosis. Therefore, the Epidemiological Investigation and Evaluation Committee concluded that the three patients' work-related exposure to heavy metals, organic solvents, and diesel exhaust is significantly supported by scientific evidence as a cause of their amyotrophic lateral sclerosis.

Distinct Longitudinal Changes in EEG Measures Reflecting Functional Network Disruption in ALS Cognitive Phenotypes.

Amyotrophic lateral sclerosis (ALS) is characterised primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. We have shown previously that resting-state EEG captures dysfunction in motor and cognitive networks in ALS. However, the longitudinal development of these dysfunctional patterns, especially in networks linked with cognitive-behavioural functions, remains unclear. Longitudinal studies on non-motor changes in ALS are essential to further develop our understanding of disease progression, improve care and enhance the evaluation of new treatments. To address this gap, we examined 124 ALS individuals with 128-channel resting-state EEG recordings, categorised by cognitive impairment (ALSci, n = 25), behavioural impairment (ALSbi, n = 58), or non-impaired (ALSncbi, n = 53), with 12 participants meeting the criteria for both ALSci and ALSbi. Using linear mixed-effects models, we characterised the general and phenotype-specific longitudinal changes in brain network, and their association with cognitive performance, behaviour changes, fine motor symptoms, and survival. Our findings revealed a significant decline in [Formula: see text]-band spectral power over time in the temporal region along with increased [Formula: see text]-band power in the fronto-temporal region in the ALS group. ALSncbi participants showed widespread ß-band synchrony decrease, while ALSci participants exhibited increased co-modulation correlated with verbal fluency decline. Longitudinal network-level changes were specific of ALS subgroups and correlated with motor, cognitive, and behavioural decline, as well as with survival. Spectral EEG measures can longitudinally track abnormal network patterns, serving as a candidate stratification tool for clinical trials and personalised treatments in ALS.

Autophagy, aging, and age-related neurodegeneration.

Autophagy is a conserved mechanism that degrades damaged or superfluous cellular contents and enables nutrient recycling under starvation conditions. Many neurodegeneration-associated proteins are autophagy substrates, and autophagy upregulation ameliorates disease in many animal models of neurodegeneration by enhancing the clearance of toxic proteins, proinflammatory molecules, and dysfunctional organelles. Autophagy inhibition also induces neuronal and glial senescence, a phenomenon that occurs with increasing age in non-diseased brains as well as in response to neurodegeneration-associated stresses. However, aging and many neurodegeneration-associated proteins and mutations impair autophagy. This creates a potentially detrimental feedback loop whereby the accumulation of these disease-associated proteins impairs their autophagic clearance, facilitating their further accumulation and aggregation. Thus, understanding how autophagy interacts with aging, senescence, and neurodegenerative diseases in a temporal, cellular, and genetic context is important for the future clinical application of autophagy-modulating therapies in aging and neurodegeneration.

Cognitive impairment in children with 5q-associated spinal muscular atrophy type 1: two case reports and the review of the literature.

Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutations in the survival motor neuron 1 (SMN1) gene on chromosome 5, leading to the degeneration of lower motor neurons. There are few studies on cognitive impairment comorbid with SMA. Here, we report two cases of severe cognitive impairment in Chinese children with SMA type 1, marking the first such reports in this demographic. We propose that severe cognitive dysfunction may be a comorbidity of SMA. Clinicians should consider SMA in patients presenting with severe muscle weakness and atrophy accompanied by cognitive impairments, to avoid misdiagnosis and oversight.

Paraneoplastic Motor Neuron Disease in a Patient With Sigmoid Colon Adenocarcinoma: A Case Report.

Paraneoplastic neurological syndromes (PNS) are a rare and diverse group of disorders caused by immune-mediated effects of malignancies. These syndromes are very rare and often present diagnostic and therapeutic challenges. Motor neuron disease as a paraneoplastic condition is particularly uncommon, especially in association with gastrointestinal malignancies like sigmoid colon adenocarcinoma. A 62-year-old male with type 2 diabetes mellitus (T2DM) presented with chronic diarrhea and a three-year history of progressive bilateral limb weakness. Initial symptoms were attributed to diabetic neuropathy, but the rapid progression and severity warranted further investigation. Neurological examination revealed hypotonia, muscle wasting, and absent reflexes in all four limbs. Diagnostic tests, including electromyography (EMG) and nerve conduction studies, confirmed motor sensory axonal neuropathy. A colonoscopy revealed a mass in the sigmoid colon, and a biopsy confirmed adenocarcinoma. The patient was managed with surgical resection of the tumor, adjuvant chemotherapy, and immunomodulatory treatments, resulting in the stabilization of neurological symptoms. This case highlights the importance of considering paraneoplastic syndromes in patients with unexplained neurological symptoms, particularly when a malignancy is suspected or known. Early recognition and a multidisciplinary approach are crucial for improving patient outcomes. Further research is needed to understand the pathophysiological mechanisms and develop sensitive biomarkers for early detection.

New developments in the diagnosis and management of motor neuron disease.

INTRODUCTION: Motor neuron disease (MND) is a devastating neurodegenerative disease characterized by progressive muscle weakness. SOURCES OF DATA: PubMed, MEDLINE, and Cochrane databases were searched for articles to March 2024. Searches involved the terms 'motor neuron disease' or 'amyotrophic lateral sclerosis' and 'epidemiology', 'diagnosis', 'clinical', 'genetic', 'management', 'treatment', or 'trial'. AREAS OF AGREEMENT: Evidence-based management involves riluzole, multidisciplinary care, provision of noninvasive ventilation and gastrostomy, and symptomatic treatments. Tofersen should be offered to treat SOD1-MND. AREAS OF CONTROVERSY: Edaravone and Relyvrio are approved treatments in the USA, but insufficient evidence was found to support approval in the UK and Europe. GROWING POINTS: The discovery of neurofilaments as MND biomarkers, growth of platform trials and development of novel therapies provide optimism for more powerful neuroprotective therapies. AREAS TIMELY FOR DEVELOPING RESEARCH: Further work should focus on the elucidation of environmental causes of MND, gene-environment interactions, and advanced cellular models of disease.

Influences of Specialist Palliative Care Team Input, Advance Care Planning, Non-Invasive Ventilation and Gastrostomy Status on Unscheduled Hospital Admissions and Place of Death for People with Motor Neuron Disease: A Retrospective Cohort Analysis.

OBJECTIVE: Motor neuron disease is a rapidly progressing neurological condition. People with life-limiting conditions generally prefer to die at home and avoid hospital admissions, with Specialist Palliative Care Team involvement often pivotal. Our aim was to investigate the role of advance care planning, Specialist Palliative Care Team input and other relevant variables on place of death and unscheduled hospital admissions in a Scottish population of people with motor neuron disease. Methods: National CARE-MND audit data, primary and secondary care data, and local Palliative Care records were interrogated. Chi-square, point-biserial correlation and binary logistic regression analysed associations (p < 0.05 statistically significant). Participants (188) were deceased, having a verified motor neuron disease diagnosis between 2015-2017, diagnosis occurring ≥28 days before death. Results: Advance care planning and Specialist Palliative Care Team input of ≥28 days were associated with increased odds of dying outside hospital (BLR:OR 3.937, CI 1.558-9.948, p = 0.004 and OR 2.657, CI 1.135-6.222, p = 0.024 respectively). Non-invasive ventilation decreased the odds of dying outside hospital (BLR:OR 0.311, CI 0.124-0.781, p = 0.013). Having a gastrostomy increased odds of ≥1 admissions in the last year of life (BLR:OR 5.142, CI 1.715-15.417, p = 0.003). Statistical significance was retained with removal of gastrostomy-related complications. Conclusion: Early Specialist Palliative Care input and advance care planning may increase the likelihood of death outside of hospital for persons with motor neuron disease. Further research is warranted into barriers of facilitating death outside of hospital with home non-invasive ventilation use and the association between gastrostomy status and unscheduled admissions.

Combination AAV therapy with galectin-1 and SOD1 downregulation demonstrates superior therapeutic effect in a severe ALS mouse model.

Neuroinflammation is a miscreant in accelerating progression of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, treatments targeting neuroinflammation alone have led to disappointing results in clinical trials. Both neuronal and non-neuronal cell types have been implicated in the pathogenesis of ALS, and multiple studies have shown correction of each cell type has beneficial effects on disease outcome. Previously, we shown that AAV9-mediated superoxide dismutase 1 (SOD1) suppression in motor neurons and astrocytes significantly improves motor function and extends survival in ALS mouse models. Despite neuron and astrocyte correction, ALS mice still succumb to death with microgliosis observed in endpoint tissue. Therefore, we hypothesized that the optimal therapeutic approach will target and simultaneously correct motor neurons, astrocytes, and microglia. Here, we developed a novel approach to indirectly target microglia with galectin-1 (Gal1) and combined this with our previously established AAV9.SOD1.short hairpin RNA treatment. We show Gal1 conditioning of SOD1 G93A microglia decreases inflammatory markers and rescues motor neuron death in vitro. When paired with SOD1 downregulation, we found a synergistic effect of combination treatment in vivo and show a significant extension of survival of SOD1 G93A mice over SOD1 suppression alone. These results highlight the importance of targeting inflammatory microglia as a critical component in future therapeutic development.

Tongue exercise ameliorates structural and functional upper airway deficits in a rodent model of hypoglossal motor neuron loss.

Introduction: Tongue weakness and atrophy can lead to deficits in the vital functions of breathing and swallowing in patients with motor neuron diseases (MNDs; e.g., amyotrophic lateral sclerosis (ALS) and pseudobulbar palsy), often resulting in aspiration pneumonia, respiratory failure, and death. Available treatments for patients with MNDs are largely palliative; thus, there is a critical need for therapies targeting preservation of upper airway function and suggesting a role for tongue exercise in patients with MNDs. Here, we leveraged our inducible rodent model of hypoglossal (XII) motor neuron degeneration to investigate the effects of a strength endurance tongue exercise program on upper airway structure and function. Our model was created through intralingual injection of cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue to induce targeted death of XII motor neurons. Methods: Rats in this study were allocated to 4 experimental groups that received intralingual injection of either CTB-SAP or unconjugated CTB + SAP (i.e., control) +/- tongue exercise. Following tongue exercise exposure, we evaluated the effect on respiratory function (via plethysmography), macrostructure [via magnetic resonance imaging (MRI) of the upper airway and tongue], and ultrafine structure [via ex vivo magnetic resonance spectroscopy (MRS) of the tongue] with a focus on lipid profiles. Results: Results showed that sham exercise-treated CTB-SAP rats have evidence of upper airway restriction (i.e., reduced airflow) and structural changes present in the upper airway (i.e., airway compression) when compared to CTB-SAP + exercise rats and control rats +/- tongue exercise, which was ameliorated with tongue exercise. Additionally, CTB-SAP + sham exercise rats have evidence of increased lipid expression in the tongue consistent with previously observed tongue hypertrophy when compared to CTB-SAP + exercise rats or control rats +/- tongue exercise. Conclusion: These findings provide further evidence that a strength endurance tongue exercise program may be a viable therapeutic treatment option in patients with XII motor neuron degeneration in MNDs such as ALS. Future directions will focus on investigating the underlying mechanism responsible for tongue exercise-induced plasticity in the hypoglossal-tongue axis, particularly inflammatory associated factors such as BDNF.

Exploring amyotrophic lateral sclerosis through the visual system: A systematic review.

BACKGROUND AND PURPOSE: The human visual system relies on neural networks throughout the brain that are easily accessible for tests exploring eye structures and movements. Over the past two decades, investigations have been carried out on both afferent and efferent components of the visual system in people with amyotrophic lateral sclerosis (ALS). This approach might represent an innovative biomarker research strategy to better characterise the phenotypic variability of ALS. The purpose of this review was to determine whether exploring the visual system of patients with ALS (pwALS) is an effective strategy. METHODS: The Medline and Web of science databases were searched for studies with terms relating to ALS and vision. Of 1146 references identified, 43 articles were included. RESULTS: In this review article, both afferent and efferent components of the visual system were found to be impaired in pwALS in the absence of visual complaint, thereby contributing to the hypothesis that ALS is a multisystem disease with sensory involvement. Of note, some areas of the eye remain unexplored (i.e., tears, and retinal function using electroretinography). CONCLUSIONS: According to the findings available in the literature, investigating the oculomotor system and exploring the ocular surface could represent two key promising strategies to identify new diagnostic biomarkers in pwALS. Further longitudinal studies are needed to identify relevant indicators of disease progression and response to therapeutic intervention.

How to break the news in amyotrophic lateral sclerosis/motor neuron disease: practical guidelines from experts.

In amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), it is necessary to communicate difficult news during the initial diagnosis and throughout the disease trajectory as the condition progresses. However, delivering difficult news to people with ALS/MND is an emotionally demanding task for healthcare and allied health professionals-one for which many feel ill-prepared because of limited training in this area. Ineffective communication of difficult news damages the patient-provider relationship and negatively impacts patient quality of life (QoL). To address this issue, we developed the A-L S-PIKES protocol based on available literature and our extensive clinical experience. It provides easy-to-follow, stepwise guidelines to effectively deliver difficult news to people with ALS/MND (PALS) that includes: Advance Preparation (preparing for the discussion logistically and emotionally); Location & Setting (creating a comfortable setting that fosters rapport); Patient's Perceptions (assessing PALS' understanding and perception of their condition); Invitation (seeking PALS' permission to share information); Knowledge (sharing information in a clear, understandable manner); Emotion/Empathy (addressing emotions with empathy and providing emotional support); and Strategy & Summary (summarizing the discussion and collaboratively developing a plan of action). A-L S-PIKES provides practical guidelines on how to prepare for and conduct these challenging conversations. It emphasizes effective communication tailored to the individual needs of PALS and their families, empathy, sensitivity, and support for PALS' emotional well-being and autonomy. The aim of A-L S-PIKES is to both enhance skills and confidence in delivering difficult news and to improve the QoL of PALS and their families. Future studies should systematically evaluate the feasibility and effectiveness of A-L S-PIKES to establish its utility in clinical practice.

Diffusion tensor imaging biomarkers and clinical assessments in amyotrophic lateral sclerosis (ALS) patients: an exploratory study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Biomarkers are needed to improve diagnosis, gauge progression, and evaluate treatment. Diffusion tensor imaging (DTI) is a promising biomarker for detecting microstructural alterations in the white matter tracts. This study aimed to assess DTI metrics as biomarkers and to examine their relationship with clinical assessments in patients with ALS. Eleven patients with ALS and 21 healthy controls (HCs) underwent 3T MRI with DTI. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were compared between key motor and extra-motor tract groups. Group comparisons and correlations between DTI metrics also correlated with clinical scores of disability (ALSFRS-R), muscle strength (dynamometry), and motor unit loss (MUNIX). Widespread differences were found between patients with ALS and HCs in DTI metrics, including decreased FA and increased diffusivity metrics. However, MD and RD are more sensitive metrics for detecting white matter changes in patients with ALS. Significant interhemispheric correlations between the tract DTI metrics were also observed. DTI metrics showed symmetry between the hemispheres and correlated with the clinical assessments. MD, RD, and AD increases significantly correlated with lower ALSFRS-R and MUNIX scores and weaker dynamometry results. DTI reveals microstructural damage along the motor and extra-motor regions in ALS patients. DTI metrics can serve as quantitative neuroimaging biomarkers for diagnosis, prognosis, monitoring of progression, and treatment. Combined analysis of imaging, electrodiagnostic, and functional biomarkers shows potential for characterizing disease pathophysiology and progression.